The proposed research is directed toward the technological understanding and improvement of therapeutic membrane plasmapheresis. It is not concerned with particular clinical reasons for using plasmapheresis. The process is considered in two parts: (1) cell-plasma separation and (2) comcomitant plasma processing to provide, for simultaneous return to the patient, a stream of endogenous plasma devoid of only selected components. Consideration of plasma processing is restricted to shema involving a membrane but possibly in conjunction with coordinated immunochemical reactions. Both process parts are to be studied in a rotational test cell as well as in prototype flow cells. Membranes for both parts, procured from commercial sources, are to be evaluated under controlled shear with well-characterized, fresh, uncolled human blood. Relationships among flux, transmembrane pressure, and shear rate are to be sought. Critical mechanisms are to be identified for each part; in the first, how shear prevents entrapment of cells in membrane pores, and, in the second, how proteins with intermediate reflection coefficients interact in finite transmembrane flows to produce observed separation factors. Hemolysis and other indications of blood damage are to be assessed for part 1. Sieving and fractionation of proteins ranging in size from albumin to immune complexes are to be studied for both parts. Process stability and optimization including policy for the addition of diluent fluids is to be studied for both parts. Staging and immunochemical schemes to enhance separation are to be studied for part 2. Emphasis is to be placed on the study of new microporous membranes for both parts including efforts to connect their physical characterization to performance. The mechanism of filtration and the role of shear, presumably different in each part is to be studied for both, with emphasis on the role of imperfections and hyperporous regions in establishing critical performance levels.